Atherosclerotic coronary artery disease (CAD) is one of the major health problems in the human population. It is positively associated with levels of low density lipoprotein cholesterol (LDL-C), intermediate density lipoprotein cholesterol (HDL-C). Recently research has focused on the role that insulin resistance plays in the establishment of coronary heart disease. It has been shown that the ability of dietary cholesterol to raise plasma cholesterol concentration in individuals with combined hyperlipidemia (increased cholesterol and triglycerides) is greater than those who have other lipid phenotypes. Individuals with combined hyperlipidemia often present with a cluster of abnormalities, which increase the risk of coronary heart disease. These abnormalities consist of higher fasting triglyceride and lower high density (HDL) lipoprotein concentrations, an enhanced degree of postprandial lipemia, smaller and denser low density lipoprotein (LDL particles, hyperuricemia, hypertension and hyperinsulinemia. Based upon our laboratory observations that subjects with combined hyperlipidemia show a greater response to dietary cholesterol, there is an excellent chance that subjects with combined hyperlipidemia show a greater response to dietary cholesterol, there is an excellent chance that subjects with insulin resistance (or a subset thereof) represent a significant fraction of the population that have an exaggerated response to dietary cholesterol. If insulin resistant individuals are most susceptible to an increase in dietary cholesterol, it seems obvious that efforts to limit cholesterol should be aimed at this group. Conversely, if insulin sensitive individuals demonstrate very little response to increases in dietary cholesterol, there is little justification for limiting cholesterol intake in such persons. In this light, understanding the causes of variations in dietary response and identifying the characteristics of dietary cholesterol responders will facilitate a more targeted approach focusing on patients who would gain the greatest plasma cholesterol lowering benefit from dietary cholesterol restrictions. This in turn will lead to rational recommendations for the American diet to the public as a whole.